Is a parental history of coronary arterial disease in children as discriminating as their lipoprotein profile?

International Journal of Cardiology, 36 (1992) 267-271 0 1992 Elsevier Science Publishers B.V. All rights reserved

CARD10

267 0167-5273/92/$0500

01509

Is a parental history of coronary arterial disease in children as discriminating as their lipoprotein profile? M. Sanchez Bayle, A. Gonzalez Vergaz, B. Garcia Cuartero, M. Santos Tapia, A. Gonzalez Requejo and the Nifio Jesus Group * Hospital del Nirio Jesus, Madrid, Spain (Received

18 October

1991; revision

accepted

15 April 1992)

Bayle MS, Vergaz AG, Cuartero BG, Tapia MS, Requejo AG, Nina Jesus Group. Is a parental history of coronary arterial disease in children as discriminating as their lipoprotein profile? Int J Cardiol 1992:36:267-271. The relationship between hyperlipidemia and a parental history of heart attack and other related disorders was studied in 2224 two- to 18-yr-old children in Madrid (Spain). Children were divided into three groups: those with a parental history of heart attack (first group), a parental history of stroke, hypertension, diabetes mellitus or hypercholesterolemia (second group), and no parental history of disease (third group). The number of children with higher than normal levels of total cholesterol ( > 200 mg/dl), LDL-cholesterol ( > 135 mg/dl) and/or apolipoprotein BlOO (> 75 mg/dl) was significantly higher in the first and second group (positive parental history1 than in the third (no parental history). Children and adolescents with a parental history of heart attack (first group) had significantly higher mean levels of total cholesterol and LDL-cholesterol; in the 2- to 13-yr age group a significantly higher level of apolipoprotein B was also found. Children and adolescents belonging to the second group had a significantly higher level of LDL-cholesterol, and a significantly higher level of apolipoprotein B was also found in the 2- to 13-yr age group. However, only 15% of children with hypercholesterolemia had a parental history of heart attack or other related disorders. This percentage was 41% when second-degree relatives were included in the family history. We conclude that a parental history is not enough to detect children with an abnormal lipid profile who might be at risk for early development of coronary arterial disease. Key words: Parental history; Cholesterol;

LDL-cholesterol;

Correspondence to: MS. Bayle, Hospital de1 Niiio Jesus, Avda Menendez Pelayo 65, 28009 Madrid, Spain. * The following Niiio Jesus Group members are co-authors of this report: C. Serna Saugan. M.A. Arias Alvarez, J. Baeza, P. Arnaiz, S. Vila. J. Asensio and C. Ruiz-Jarabo (Pediatrics and laboratory services, Hospital Del Niiio Jesus). This study was supported by the Social Work of Caja Madrid.

Apolipoprotein

B

Introduction The high prevalence of cardiovascular disease in industrialized nations and its relation to hypercholesterolemia, the presence of fatty streaks in vessel walls in the early ages of life and the tracking of cholesterol concentrations in child-

268

hood into adult life have highlighted the need to identify children and adolescents with hypercholesterolemia who might be at risk for the early development of atherosclerosis and subsequent coronary arterial disease [l-4]. Two different courses of action have been proposed to detect children at risk: either to perform screening of all children for blood cholesterol concentration or to carry out such screening only in subjects with a parental history of cardiovascular disease [5-71. This work attempts to study the relationship between abnormal blood lipids and parental history, and then to assess the value of family history as a means of detecting children at risk for the early development of coronary arterial disease. Subjects and Methods A total of 2224 children and adolescents of both sexes from several schools in Madrid city and its outskirts were included in our study. A parental history of heart attack, stroke, diabetes mellitus, hypertension or hypercholesterolemia was obtained through questionnaires completed by both parents. Venous blood was taken after an overnight fast (minimum 10 h). Serum was obtained and tested for lipids, lipoprotein cholesterols and apolipoproteins A and B. Laboratory procedures Triglycerides and total cholesterol were measured by an enzymatic method using a commercial kit (Boehringer Mannheim, Germany) [81. HDL-

TABLE

1

Number

of children

with a parental

history

Mother

Father No. Heart attack Stroke Hypertension Diabetes mellitus Hypercholesterolemia No. of subjects

60 9 91 11 152 279

of disease.

‘% 2.7 0.4 4.1 0.5 6.8

No.

%

50 0 80 35 57 211

2.2 3.6 1.6 2.6

’

cholesterol was determined in the supernatant obtained after precipitation of VLDL- and LDLcholesterol by phosphotungstate-Mg2fC1[9]. LDL-cholesterol was calculated according to the formula of Friedewald [lo]. Apolipoproteins A and B were determined, using specific antibodies, by kinetic nephelometry in an Array protein system kit (Beckman Instruments Inc). Statistical analysis Sensitivity and specificity were calculated through the use of “parental history of vascular disease” as a test to detect children with abnormal lipid levels. To calculate the predictive value of a positive test, the presence of hyperlipidemia was used as the standard (denominator) [ 111. Data were processed by a Norgate 286 PC compatible computer and analysed by the SPSS commercial pack. Results Children and adolescents were divided in 3 groups: parental history of heart attack (first group), parental history of stroke, hypertension, diabetes mellitus or hypercholesterolemia (second group), and no parental history of disease (third group). 328 subjects (14.7%) were found to have a positive parental history, 110 belonged to the first group and 218 to the second one. Children who had a parental history of heart attack and any other disease were included in the first group (Table 1). As shown in Table 2, children from 2 to 13 yr whose father or mother reported having had a heart attack had significantly higher mean levels of total cholesterol, LDL-cholesterol and apolipoprotein B. Adolescents belonging to the same group (13-18 years) had similar results, although statistically significant differences were only found for total cholesterol and LDLcholesterol. Children with a parental history of stroke, hypertension, diabetes mellitus or hypercholesterolemia had significantly higher levels of LDL-cholesterol and apolipoprotein B. In adolescents, significant differences were only found for LDL-cholesterol.

269 TABLE

2

Blood lipids and apolipoproteins:

mean values

and standard

deviations.

2-13 years

Total chol. HDL-chol. LDL-chol. VLDL-chol. Trigl. Apo A Apo B Number * p HA OD ND

< = = =

14-18 years

HA

OD

ND

HA

OD

ND

189 * 25 52 10 121 * 14 13 4 60 20 130 22 72 * 12 42

180 20 55 10 120 * 20 14 4 61 18 128 20 71 * 10 84

175 25 55 12 106 20 12 5 58 20 135 28 63 12 1118

173 * 27 55 10 122 * 25 13 6 62 31 139.5 23 58 14 68

171 * 26 54 11 123 * 26 12.5 7 61 22 138 26 57 20 134

166 23 56 12 100 28 I’ ; 60.5 20 136.5 36 56 12 817

0.05. parental history of heart attack; parental history of other diseases (stroke, hypertension, diabetes mellitus and/or hypercholesterolemia); no parental history of disease; chol. = cholesterol; Trigl. = triglyceride; Apo = apolipoprotein.

Table 3 shows the number of subjects with abnormal lipid levels in each group. Children and adolescents from the first and second group (positive parental history) had more frequently

TABLE

3

Number

of subjects

with hyperlipidemia HA

No. of subjects Total chol. > 200 mg/dl LDL-chol. > 135 mg/dl Apo B > 75 mg/dl HDL-chol. < 35 mg/dl

110

in the different

higher than normal levels of total cholesterol, LDL-cholesterol and apolipoprotein B than subjects from the third group (no parental history of cardiovascular disease).

groups. OD

ND

Total

218

1896 364 (13.9) 190 (10) 191

2 224 337 (15.1) 247 (11.1) 241 (10.8) 42

* $7) 22 *

(z)*

(20) 20 ** (18.2) 2NS

c;:,* 30** (13.8) 4 NS

(1.8)

(1.8)

* p < 0.001. * * p < 0.05. NS = not significant. HA = parental history of heart attack. OD = parental history of other diseases (stroke, hypertension, diabetes and/or ND = no parental history of disease. Values in parentheses are percentages.

(10) 36 (1.9)

hypercholesterolemia).

(1.9)

270 TABLE Evaluation

4 of a positive

parental

history

as a test to detect

Sensitivity

an abnormal

lipid profile

Specificity

in children.

PPV

Odds ratio

HA

OD

HA

OD

HA

OD

HA

OD

Total cholesterol > 200 mg/dl

1.4

14.2

95.5

90.1

22.1

22.0

1.69

1.67

LDL cholesterol > 135 mg/dl

8.9

14.2

95.5

90.7

20.0

16.0

2.09

1.61

Apolipoprotein B 100 > 75 mg/dl

8.3

12.4

95.5

90.5

18.2

13.8

1.90

1.35

diabetes,

hypertension

HA = parental history of heart positive predictive value

attack:

OD = parental

history

We. have evaluated parental history as a test to detect hyperlipidemia in children. Results are shown in Table 4. Although specificity is fairly high ( > 90%0), the test lacks sensitivity: > 80% of children with high total cholesterol and/or high LDL-cholesterol and/or high apolipoprotein B had no parental history of disease. 85% of these children were reevaluated ‘later on, and a positive familial history in second-degree relatives was found in 40.5%. :

Discussion It is well known that the risk of cardiovascular disease is related to high blood levels of total cholesterol, LDL-cholesterol and apolipoprotein B. These high levels can be detected in early ages of life. As longitudinal studies have demonstrated, high blood lipid levels in childhood may remain high in adulthood. Thus it is possible to detect during childhood individuals who would be at risk for cardiovascular disease in their adult life [12-151. The screening of all children for cholesterol concentration has been questioned because of its high cost. Moreover, many studies, both in infants and older children, have shown that dietary changes can reduce plasma cholesterol and may then delay or prevent the development of the atherosclerotic process. Moreover, reduction in cholesterol levels has been described in school

of stroke,

or hypercholesterolemia;

PPV =

groups after the implementation of educational programmes [16-181. Some authors have suggested that total cholesterol and triglycerides determinations should be performed for all 2-yr-old children, and later between 10 and 15 yr of age [4,5]. Other authors have proposed performing cholesterol screenings only in children with a parental history of cardiovascular disease, on the basis that such group has higher cholesterol levels [6]. In our study, subjects with either a parental history of heart attack or a parental history of stroke, hypertension, diabetes mellitus or hypercholesterolemia had higher mean levels of total cholesterol, triglycerides, LDLcholesterol and apolipoprotein B along with lower mean levels of LDL-cholesterol and apolipoprotein A, although some of the differences were not statistically significant. Moreover, the number of subjects with abnormal lipid levels was significantly higher in both groups with a positive parental history. These rest&s are similar to those found by other authors [6,15,19]. However, children with a positive parental history accounted for only 21.7% of children with higher than normal levels of total cholesterol and/or LDL-cholesterol. If we were to take into account the presence of cardiovascular disease in second-degree relatives, the percentage would be 40.6%. Griffin [15] has recently found that children with a positive familial history represented 51% of subjects with a high LDL-cholesterol level.

771

LDL-cholesterol has been found to be the best parameter to evaluate lipid abnormalities [19]. From our study we infer that parental history is not a reliable means of detecting children and adolescents with hypercholesterolemia. More active policies are needed, such as educational programs focused on changing the dietary habits of the general population or the implementation of a systematic method of identifying lipid alterations in children in which routine blood studies are performed as has been suggested by the American Heart Association and European Atherosclerosis Society [.5,201.

7

8

9

10

I1

Acknowledgements We are grateful to M.J. Aguilera, A. Aranguren, C. Benito, P. Cabello, L. Fernandez, C. Garcia, M.T. Gonzalez, C. Huertas, C. Lopez, E. Ponce de Leon and M. Porras, nurses and laboratory technicians from Nifio Jesus Children Hospital for their help in data collection and sample processing. References Gondon T. Castelli WP. Hjortland MC. Kannel WB, Dawber TR. High density lipoprotein as a predictive factor against coronary heart disease. The Framingham study. Am J Med 1972;62:707-714. McGill HC Jr. Morphologic development of the atherosclerosis plaque. In: Lauer RM, Shkelle RB. eds. Childhood prevention of atherosclerosis and hypertension. New York: Raven Press, 1980. Freedman DS, Shear CL, Srinivasan SR. Tracking of serum lipids and lipoproteins in children over B-years period: the Bogalusa heart study. Prevent Med 1985:14:203-216. Nora JJ. Identifying the child at risk for coronary disease as an adult: a strategy for prevention. J Pediatr 1980:97:706-714. Committee on Atherosclerosis and Hypertension in Childhood of the Council of Cardiovascular Disease in the Young and the Nutrition Committee, American Heart Association: Diagnosis and Treatment of Primary Hyperlipidemia in Childhood. Circulation 1986;74:1181-1188A. Dennison BA, Kikuchi DA, Srinivasan SR, Webber L, Berenson G. Parental history of cardiovascular disease as

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an indicator for screening for lipoprotein abnormalities in children. J Pediatr 3989;115:186-194. Committee on nutrition. American Academy of Pediatrics: indications for cholesterol testing in children. Pediatrics 1989:83:141-142. Siedel J, Schlumberger H, Klose S. Ziegen J. Horn J, Wahlefeld AW. Improved reagent for the enzymatic determination of serum cholesterol. J Chem Clin Biochem 1981:19:838-839. Assman G. Schiewer H, Schnitz G, Haegele D. Quantification of high density lipoprotein cholesterol by precipitation with phosphotungstic acid-MG-CL2 Clin Chem 1983;29:2026-2030. Fiedewald WT, Levy RI. Fredrickson DS. Estimation of the concentration of C-LDL in plasma without use of the preparative ultracentrifuge. Clin Chem 1972,1X:499-507. Fletcher RH, Fletchar SW, Wagner EC. Clinical epidemiology: the essentials. Baltimore: Williams & Wilkins, 1982;46-52. Moll PP, Sing CF. Weidman WH. Total cholesterol and lipoproteins in school children: prediction of coronary heart disease in adults relatives. Circulation 1983:67:127134. NIH Consensus Development Conference Statement. Lowering blood cholesterol to prevent heart disease. JAMA 1985,253:2080-2086. Berenson GS. MC Mahan CA, Voors AW. Cardiovascular risk factors in children: the early natural history of atherosclerosis and essential hypertension. New York: Oxford University Press, 1980. Griffin TC, Christoffel KK. Binns HJ, MC Guire PA. Pediatric Practice Research Group. Family history evalua tion as a predictive screen for childhood hypercholesterolemia. Pediatrics 1989;84:365-373. Schrott HG, Clarke WR. Wiebe DA, Conor WE, Lauer RM. Increased coronary mortality in relatives hypercholesterolemic school children: the muscatine study. Circulation 1979;59:320-326. Khaw K-T. Rose G. Cholesterol screening programmes: how much potential benefit? Br Med J 1989;299:606-607. Walter HJ. Hofman H, Vaughan RD, Wynder EL. Modification of risk factors for coronary heart disease. N Engl J Med 1988;318:1093-1100. Kwiterovich PO, Heiss G, Johnson N, Chase GA, Tamir I, Rifkind B. Assessment of plasma total cholesterol as a test to detect elevated low density (beta) lipoprotein cholesterol levels (type IIa hyperlipoproteinemia) in young subjects from a population-based sample. Am J Epidemiol 1982;115:192-204. Study group, European Atherosclerosis Society. Strategies for the prevention of coronary heart disease: a policy statement of the European Atherosclerosis Society. Eur Heart J 1987$+77-X8.